title: Postnatal dietary fatty acid composition permanently affects the structure of hypothalamic pathways controlling energy balance in mice.
abstract: BACKGROUND
  We previously reported that dietary lipid quality during early life can have long-lasting effects on metabolic health and adiposity. Exposure to a postnatal diet with low dietary omega-6 (n-6) or high omega-3 (n-3) fatty acid (FA) content resulted in reduced body fat accumulation when challenged with a moderate Western-style diet (WSD) beginning in adolescence.
  
  
  OBJECTIVE
  We determined whether this programming effect is accompanied by changes in hypothalamic neural projections or modifications in the postnatal leptin surge, which would indicate the altered development of hypothalamic circuits that control energy balance.
  
  
  METHODS
  Neonatal mice were subjected to a control diet (CTR) or experimental diet with altered relative n-6 and n-3 FA contents [ie, a diet with a relative reduction in n-6 fatty acid (LOW n-6) or a diet with a relative increase in n-3 fatty acid (HIGH n-3) compared with the CTR from postnatal day (PN) 2 to 42].
  
  
  RESULTS
  Compared with CTR mice, mice fed a LOW n-6 or HIGH n-3 during postnatal life showed significant reductions in the density of both orexigenic and anorexigenic neural projections to the paraventricular nucleus of the hypothalamus at PN 28. These impairments persisted into adulthood and were still apparent after the WSD challenge between PNs 42 and 98. However, the neuroanatomical changes were not associated with changes in the postnatal leptin surge.
  
  
  CONCLUSIONS
  Although the exact mechanism remains to be elucidated, our data indicate that the quality of dietary FA during postnatal life affects the development of the central regulatory circuits that control energy balance and may do so through a leptin-independent mechanism.
authors.affiliation: From Nutricia Research - Danone Nutricia Early Life Nutrition, Utrecht, Netherlands (LS and AO); the Neuroscience Program, The Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA (KB and RBS); and Nutricia Research - Danone Nutricia Early Life Nutrition, Singapore (EMvdB).
authors.forename: Lidewij
authors.initials: L
authors.lastname: Schipper
authors.forename: Karine
authors.initials: K
authors.lastname: Bouyer
authors.forename: Annemarie
authors.initials: A
authors.lastname: Oosting
authors.forename: Richard B
authors.initials: RB
authors.lastname: Simerly
authors.forename: Eline M
authors.initials: EM
authors.lastname: van der Beek
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001069:Appetite Regulation; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D001522:Behavior, Animal; D004734:Energy Metabolism; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D007774:Lactation; D020738:Leptin / Q000097:blood / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D011897:Random Allocation; D015854:Up-Regulation
chemical_list: D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D020738:Leptin